Background& Aims: Hepatitis B virus (HBV) DNA
detection in serum and/or in the liver of hepatitis B
surface antigen (HBsAg)-negative patients with or
without serologic markers of previous viral exposure
is defined as occult HBV infection. Because the role of
the adaptive response in keeping HBV replication
under control in occult infection still is undefined,
this study was performed to characterize the features
of the HBV-specific T-cell response in this condition.
Methods: HBV-specific T-cell frequency and function
were tested ex vivo and after in vitro expansion in 32
HBsAg-negative patients undergoing diagnostic liver
biopsy for chronic hepatitis C: 18 with occult HBV
infection (11 anti-HBc–negative and 7 anti-HBc–positive
patients) defined by the detection of intrahepatic
HBV DNA by polymerase chain reaction; 14 without
detectable intrahepatic HBV DNA (5 anti-HBc–positive
and 9 anti-HBc–negative patients). Six patients
with chronic hepatitis B and 7 HBsAg-inactive carriers
were studied for comparison. Results: The presence
or absence of serologic HBV markers defined 2
profiles of HBV-specific T-cell responses in occult
infection. Anti-HBc–positive patients showed a T-cell
response typical of protective memory, suggesting
that this condition represents a resolved infection
with immune-mediated virus control. In contrast,
HBV-specific T cells in anti-HBc–negative patients
did not readily expand and produce interferon- in
vitro, suggesting the possibility of a low-dose infection
insufficient to allow maturation of protective
memory. Conclusions: Our results suggest different
mechanisms of control of viral replication in seropositive
and seronegative occult infections. Additional
studies aimed at understanding possible different
clinical implications are needed.

Background& Aims: Hepatitis B virus (HBV) DNA
detection in serum and/or in the liver of hepatitis B
surface antigen (HBsAg)-negative patients with or
without serologic markers of previous viral exposure
is defined as occult HBV infection. Because the role of
the adaptive response in keeping HBV replication
under control in occult infection still is undefined,
this study was performed to characterize the features
of the HBV-specific T-cell response in this condition.
Methods: HBV-specific T-cell frequency and function
were tested ex vivo and after in vitro expansion in 32
HBsAg-negative patients undergoing diagnostic liver
biopsy for chronic hepatitis C: 18 with occult HBV
infection (11 anti-HBc–negative and 7 anti-HBc–positive
patients) defined by the detection of intrahepatic
HBV DNA by polymerase chain reaction; 14 without
detectable intrahepatic HBV DNA (5 anti-HBc–positive
and 9 anti-HBc–negative patients). Six patients
with chronic hepatitis B and 7 HBsAg-inactive carriers
were studied for comparison. Results: The presence
or absence of serologic HBV markers defined 2
profiles of HBV-specific T-cell responses in occult
infection. Anti-HBc–positive patients showed a T-cell
response typical of protective memory, suggesting
that this condition represents a resolved infection
with immune-mediated virus control. In contrast,
HBV-specific T cells in anti-HBc–negative patients
did not readily expand and produce interferon- in
vitro, suggesting the possibility of a low-dose infection
insufficient to allow maturation of protective
memory. Conclusions: Our results suggest different
mechanisms of control of viral replication in seropositive
and seronegative occult infections. Additional
studies aimed at understanding possible different
clinical implications are needed.